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Simvastatin

Simvastatin

Zocor Flolipid Simvahexal Simvacor Simvar

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Updated: December 06, 2025

Overview

Simvastatin is a potent lipid-lowering agent in the statin class, widely used for managing hypercholesterolemia and reducing cardiovascular risk. It works by competitively inhibiting HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis. Clinical studies demonstrate its effectiveness in reducing LDL cholesterol by 25-50%, triglycerides by 10-30%, and modestly increasing HDL cholesterol. It has proven cardiovascular benefits in both primary and secondary prevention settings, particularly in high-risk patients.

Drug Class

HMG-CoA reductase inhibitor (statin) Therapeutic category: Lipid-lowering agent

Mechanism of Action

Competitively inhibits HMG-CoA reductase, the rate-limiting enzyme in cholesterol biosynthesis in the liver. This leads to: • Reduced hepatic cholesterol synthesis • Upregulation of LDL receptors on hepatocytes • Increased clearance of LDL and VLDL particles from circulation • Moderate reduction in triglyceride levels • Slight increase in HDL cholesterol levels

Pharmacokinetics

Absorption: Well absorbed orally (60-85% bioavailability), significantly reduced by food Distribution: Extensive tissue distribution, 95% protein-bound Metabolism: Hepatic metabolism via CYP3A4 isoenzyme system to active (beta-hydroxy acid) and inactive metabolites Excretion: 60% fecal excretion, 13% renal excretion Half-life: 2-3 hours for parent drug, 1.9 hours for active metabolite

Pharmacodynamics

• Dose-dependent reduction in LDL cholesterol (maximal effect at 6 weeks) • Modest reduction in triglycerides (10-30%) • Small increase in HDL cholesterol (5-10%) • Improves endothelial function • Exhibits pleiotropic effects including anti-inflammatory and plaque stabilization properties

Indications

• Primary hyperlipidemia: For reduction of elevated total cholesterol, LDL-C, apo B, and triglycerides in patients with primary hyperlipidemia • Mixed dyslipidemia: As an adjunct to diet in patients with elevated triglyceride levels • Cardiovascular risk reduction: In patients with coronary heart disease, diabetes, or other high-risk conditions to reduce cardiovascular events • Homozygous familial hypercholesterolemia: As an adjunct to other lipid-lowering treatments

Contraindications

Absolute: • Active liver disease or unexplained persistent elevations in serum transaminases • Pregnancy • Hypersensitivity to simvastatin Relative: • Concurrent use with strong CYP3A4 inhibitors • History of liver disease • Excessive alcohol consumption • Renal impairment • Asian patients (may require lower doses)

Dosage & Administration

Hyperlipidemia: Initial dose 10-20 mg once daily in evening, may increase to maximum 40 mg daily Cardiovascular risk reduction: 20-40 mg daily Homozygous familial hypercholesterolemia: 40 mg daily in evening Concurrent cyclosporine or danazol use: Do not exceed 10 mg daily Concurrent amiodarone, verapamil, or diltiazem use: Do not exceed 20 mg daily

Special Populations

Pediatric: Safety and efficacy established for adolescents 10-17 years with heterozygous familial hypercholesterolemia Geriatric: No dose adjustment needed but increased risk of myopathy Renal impairment: Dose adjustment not necessary for mild-moderate impairment; use caution in severe impairment Hepatic impairment: Contraindicated in active liver disease; avoid in severe impairment

Adverse Effects

Common (>10%): • Headache • Myalgia (muscle pain) • Constipation • Abdominal pain • Nausea Serious (<1%): • Rhabdomyolysis • Hepatotoxicity • Myopathy • Immune-mediated necrotizing myopathy • Increased HbA1c and fasting glucose

Drug Interactions

• CYP3A4 inhibitors (e.g., ketoconazole, erythromycin): Increase simvastatin levels • Cyclosporine: Increases risk of myopathy • Gemfibrozil: Increases risk of myopathy • Warfarin: May enhance anticoagulant effect • Grapefruit juice: Increases serum concentrations • Niacin: May increase risk of myopathy

Warnings & Precautions

• Risk of myopathy/rhabdomyolysis (dose-related) • Monitor liver enzymes before and during treatment • May increase blood glucose and HbA1c levels • Use caution in patients with predisposing factors for renal failure • Discontinue if markedly elevated CPK levels or myopathy diagnosed • Avoid concurrent use with strong CYP3A4 inhibitors

Pregnancy & Lactation

Pregnancy: Category X - Contraindicated due to fetal harm. Discontinue immediately if pregnancy occurs. Lactation: Contraindicated - excreted in breast milk with potential for serious adverse reactions in nursing infants.

Monitoring Parameters

• Lipid profile at baseline, 6-8 weeks after initiation, and periodically thereafter • Liver function tests at baseline and as clinically indicated • CPK levels in patients with muscle symptoms • Blood glucose monitoring in diabetic patients • Renal function in patients at risk

Patient Counseling

• Take in the evening for optimal effect • Maintain cholesterol-lowering diet during treatment • Report unexplained muscle pain/tenderness/weakness immediately • Avoid grapefruit products • Inform all healthcare providers about simvastatin use • Do not discontinue without medical advice • Discuss alcohol consumption with provider

Storage & Stability

Store at 20-25°C (68-77°F), protect from light and moisture. Keep container tightly closed. Stable for 3 months when stored at 15-30°C in original packaging.

Clinical Pearls

• Higher doses (80 mg) associated with increased myopathy risk - now rarely used • More potent statins available for patients needing >50% LDL reduction • Consider alternate dosing in Asian patients due to increased exposure • Monitor for diabetes in high-risk patients • Temporary discontinuation may be needed for major surgery

References

• UpToDate: Simvastatin Drug Information • FDA Prescribing Information for Zocor • American College of Cardiology/American Heart Association Guideline on the Treatment of Blood Cholesterol (2018) • Scandinavian Simvastatin Survival Study (4S) Trial • Heart Protection Study (HPS)